epiCaPture: a urine DNA methylation test for early detection of aggressive prostate cancer

Eve O'Reilly, Alexandra Tuzova, Anna Walsh, Niamh Russell, Odharnaith O’Brien, Sarah Kelly, Odharna Dhomhnallain, Liam DeBarra, Connie Dale, Rick Brugman, Gavin Clarke, Olivia Schmidt, Shane O'Meachair, Dattatraya Patil, Kathryn Pellegrini, Neil Fleshner, Julia Garcia, Fang Zhao, Stephen Finn, Robert MillsMarcelino Y. Hanna, Rachel Hurst, Elizabeth McEvoy, William Gallagher, Rustom Manecksha, Colin Cooper, Daniel Brewer, Bharati Bapat, Martin Sanda, Jeremy Clark, Antoinette Perry

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22 Citations (Scopus)
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Abstract

Purpose Liquid biopsies that noninvasively detect molecular correlates of aggressive prostate cancer (PCa) could be used to triage patients, reducing the burdens of unnecessary invasive prostate biopsy and enabling early detection of high-risk disease. DNA hypermethylation is among the earliest and most frequent aberrations in PCa. We investigated the accuracy of a six-gene DNA methylation panel (Epigenetic Cancer of the Prostate Test in Urine [epiCaPture]) at detecting PCa, high-grade (Gleason score greater than or equal to 8) and high-risk (D'Amico and Cancer of the Prostate Risk Assessment] PCa from urine. Patients and Methods Prognostic utility of epiCaPture genes was first validated in two independent prostate tissue cohorts. epiCaPture was assessed in a multicenter prospective study of 463 men undergoing prostate biopsy. epiCaPture was performed by quantitative methylation-specific polymerase chain reaction in DNA isolated from prebiopsy urine sediments and evaluated by receiver operating characteristic and decision curves (clinical benefit). The epiCaPture score was developed and validated on a two thirds training set to one third test set. Results Higher methylation of epiCaPture genes was significantly associated with increasing aggressiveness in PCa tissues. In urine, area under the receiver operating characteristic curve was 0.64, 0.86, and 0.83 for detecting PCa, high-grade PCa, and highrisk PCa, respectively. Decision curves revealed a net benefit across relevant threshold probabilities. Independent analysis of two epiCaPture genes in the same clinical cohort provided analytical validation. Parallel epiCaPture analysis in urine and matched biopsy cores showed added value of a liquid biopsy. Conclusion epiCaPture is a urine DNA methylation test for high-risk PCa. Its tumor specificity out-performs that of prostate-specific antigen (greater than 3 ng/mL). Used as an adjunct to prostate-specific antigen, epiCaPture could aid patient stratification to determine need for biopsy.

Original languageEnglish
Pages (from-to)1-18
JournalJCO Precision Oncology
Volume3
Issue number3
Early online date14 Jan 2019
DOIs
Publication statusPublished - 2019

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